Diffuse neuroendocrine system

the origin of cells of DNES

ectodermal, mezodermal, entodermal

DNES is divided

-peripheral (in organs): Leydig cells of testis, neuroendocrine cells of gastrointestinal and respiratory system
- neurogen: parafollicular C cells in thyroid gland, chromaffin cells of adrenal medulla, cells of adenohypophysis, pinealocytes in pineal gla

Characterization of DNES

Cells of DNES can be dispersed individually or form clusters - neuroepithelial bodies
Morphologically cells of DNES are characterized by well-developed rough endoplasmatic reticulum and Golgi apparatus, numerous mitochondria and basally located secretory

types of DNES cells

1. open - connecting with the organ lumen through an apical cytoplasmic process;
2. closed - being shorter, which do not reach the apical surface.
Still, stimulus comes basally to both type of cells. (neuron, endocrine)
in both the stimulus brings exocyto

main hormones of DNES

1. VIP
2. Tachykinin peptides
3. Calcitonin gene related peptide (CGRP)
4. Neuropeptide Y (NPY)
5. Gastrin-releasing peptide (GRP), a bombesin-like neuropeptide (bombesin)
6. Granins (chromogranin and secretogranin)
7. General DNES markers
8. Enkephalins

Vasoactive intestinal peptide VIP and related peptides

1. VIP
2. Helodermin
3. Pituitary adenylate cyclase-activating polypeptide (PACAP)

VIP

localization: only in nerve fibers, namely:
1. in blood vessel wall,
2. in ganglion,
3. between smooth muscle cell bundles,
4. around mixed glands.
functions:
1. dilatation of blood vessels,
2. smooth muscle relaxation,
3. stimulate secretion of water int

helodermin

has similar structure and effect as VIP

Pituitary adenylate cyclase-activating polypeptide (PACAP)

PACAP is widely distributed in the brain and peripheral organs, notably in the endocrine pancreas, gonads, and respiratory and urogenital tracts.
PACAP has been found to exert pleiotropic effects including modulation of neurotransmitter release, vasodilat

Tachykinin peptides

1. substance P,
2. neurokinin A,
3. neurokinin B

Substance P

localization: in nerve fibers between and beneath epithelial cells, between smooth muscle cells, in the walls of blood vessels, around parasynphatic ganglia and glandular alveolae, in the synovial membranes
functions: promote contraction of smooth muscles

the tachykinins in airways when released, effects

They may be released by a variety of stimuli (e.g. cigarette smoke, ozone) and have various effects including
smooth muscle contraction,
facilitation of cholinergic neurotransmission, submucosal gland secretion,
vasodilatation,
increase in vascular permea

Calcitonin gene-related peptide (CGRP) localization

localization: nerve fibers and neuroendocrine cells; in the epithelium or beneath them, in the wall of blood vesels and between the bundles of smooth muscle cells
It is widespread in the heart, lung, gastrointestinal tract and has a wide array of biologic

CGRP

released CGRP has the ability to degranulate mast cells and release various chemical mediators triggering inflammatory cycle.
nerve fibers projecting into the airways and pulmonary neuroendocrine cells release CGRP into lungs. In the airways, the peptide

Neuropeptide Y

localization: nerve fibers around blood vessels and glands, between smooth muscle cells
functions: contraction of smooth muscle and blood vessels
NPY controls hunger, thirst, fatigue, and body temperature; plays a role in various basic processes in the br

Bombesin

localization: in nerve fibers and in neuroendocrine cells around blood vessels and glands, in epithelium and neuroepithelial bodies
functions: regulator of numerous gastrointestinal functions, including the release of gastrointestinal hormones, smooth mus

Chromogranins/ secretogranins

includes chromogranins A (CgA) and B (CgB) and secretogranin II
localization: secretory granules of a wide variety of endocrine and neuro-endocrine cells
general markers of neuroendocrine cells (they control the packaging of hormones and the formation of

General markers of DNES

localization: all neuroendocrine cells and neuropeptides- containing nerve fibers
functions: ... still investigated
protein gene product 9.5 (PGP 9.5). The protein is highly conserved and localized in neurones and neuroendocrine cells in vertebrates, form

Endorfins, enkephalins

group of peptide hormones - endogenous opioid - that bind to opiate receptors and are found mainly in the brain.
reduce the sensation of pain and affect
emotions.

Orexins

Orexin is a neuropeptide which is released by the posterior lateral hypothalamus, and is linked to wakefulness and sleep, appetite regulation, and the motivation of sexual and addictive behaviors

Other neuropeptides

1. galanin: predominantly located in the
central nervous system and gastrointestinal tract.
2. neurotensin: stimulate histamine release from mast cells

Biogenic amines

Group of biologically active amines, such as histamine, and serotonin, that act primarily as neurotransmitters and are capable of affecting mental functioning and of regulating blood pressure, body temperature, and other bodily processes.

Neurogenic inflammation

is inflammation arising from the local release from nerve fibers of neuropeptides
such as Substance P and Calcitonin Gene-Related Peptide

Possible neurogenic inflammation

in asthmatic airways via retrograde release of peptides from nerve fibers. Substance P (SP) causes vasodilatation, plasma exudation, and mucus secretion, whereas neurokinin A (NKA) causes bronchoconstriction and enhanced cholinergic reflexes, and calciton